Heparan sulfate (HS), which is degraded by
heparanase, plays an important role in cell adhesion, insolubility of the extracellular matrix (ECM) and as a reservoir for various
growth factors such as
basic fibroblast growth factor (bFGF) and
vascular endothelial growth factor (
VEGF). In the present study, we examined the immunohistochemical expression of
heparanase, bFGF and
VEGF, and evaluated the correlation between their expression and microvessel density (MVD) in human esophageal
carcinomas.
Heparanase, bFGF and
VEGF were immunolocalized predominantly to the
carcinoma cells, but they were also localized to the endothelial cells of microvessels near the
carcinoma cell nests. In
carcinomas with invasion of the muscular layer or adventitia,
heparanase staining was stronger at the invasive areas of
carcinomas than the intraepithelial spread. Expression of
heparanase and bFGF and the degree of MVD were associated with
tumor invasion,
lymph node metastasis and pathological stages. Cases with positive staining for
heparanase, bFGF or
VEGF tended to have a higher MVD than those without staining, and
carcinomas with concomitant expression of
heparanase, bFGF and
VEGF showed the highest MVD. The level of
heparanase mRNA expression was directly correlated with the MVD. In addition,
heparanase-positive cases had a higher positive ratio of bFGF and
VEGF compared with the
heparanase-negative cases. These data suggest the possibility that
heparanase may contribute to not only
cancer cell invasion but also angiogenesis probably through degradation of HS in the ECM and release of bFGF and
VEGF from the HS-containing ECM.